Approximately 37-50% of HIV positive individuals suffer from depression, which is associated with substance use, poor adherence to HIV medication, an increase in HIV risk behaviors, and subsequent poor health outcomes (e.g., Asch et al., 2003;Bing et al., 2001;Dew et al., 1997;Johnson, Rabkin, Lipsitz, Williams, &Remien, 1999). Additionally, depressed HIV positive substance users are at an even greater risk for poor medication adherence than non-substance users (Cook, Grey, &Burke-Miller, 2004). Notably, evidence indicates that HIV positive patients who receive treatment for depression exhibit significant improvements in HIV medication adherence and a reduction in risk behaviors that are directly relevant to their health and well being such as risky sexual behavior (e.g., Cook et al., 2006). Despite this link, few interventions targeting depression have been developed to meet the specific needs of HIV-infected substance users. This is especially evident for low income African American HIV positive substance users who often do not receive adequate treatment for any of these conditions due to poverty, lack of access to specialized treatment, low motivation, cognitive impairments, and a lack of coordination between medical, mental health, and substance abuse treatment providers (Calsyn et al., 2004). Thus, the objective of the present proposal is to test a novel, behavioral approach to treat depressive symptoms and improve HIV medication adherence and subsequent physical health outcomes among 170 African American HIV infected substance users residing in inner-city Washington, DC. This treatment combines (1) LET'S ACT, a behavioral activation based treatment for depressed substance users (Daughters, Braun, Sargeant, Hopko, Blanco, &Lejuez, in press), with (2) Life Steps, an HIV medication adherence intervention (Safren, Otto, &Worth, 1999). The purpose of this combined treatment (i.e., ACT HEALTHY;see Appendix for the preliminary therapist and patient manuals), will be to compliment standard residential and follow-up outpatient substance use treatment to specifically treat depressive symptoms with the additional goal of improving HIV medication adherence, substance use, and physical health outcomes. One hundred and seventy HIV positive minority substance users with elevated depressive symptoms will be randomly assigned to either treatment as usual (TAU) plus ACT HEALTHY or TAU plus Nondirective Therapy to test the efficacy of ACT HEALTHY. Treatment as usual for both groups consists of standard residential and outpatient substance abuse treatment. Based on the outcome of this preliminary trial, the ACT HEALTHY protocol will be further refined and readied for larger-scale clinical trials. PUBLIC HEALTH RELEVANCE The objective of the present proposal is to test a novel, behavioral approach to treat depressive symptoms and improve HIV medication adherence and subsequent physical health outcomes among African American HIV infected substance users residing in inner-city Washington, DC. This treatment will serve as a compliment to standard residential and follow-up outpatient substance use treatment, with the goal of reducing depressive symptoms and improving HIV medication adherence, physical health, and substance use outcomes. From a longer term perspective, this grant will set the stage for more large-scale testing to determine its utility as a specialized, efficacious treatment for a significant subpopulation at greatest risk for difficulties with depressive symptoms, HIV medication adherence, and relapse to substance use, and will therefore have important clinical and public health significance in reducing HIV transmission.